Perhalocoumalin derivatives

ABSTRACT

A COMPOUND SELECTED FROM THE GROUP CONSISTING OG COMPOUNDS OF THE FORMULA   (R)N-Z-CO-CH(-Z-(R)N)-C(-X)=C(-X)-CO-Z(-R)N   WHEREIN X IS A HALOGEN CHOSEN FROM THE GROUP CONSISTING OF FLUORINE, CHLORINE, BROMINE, AND IODINE, AND MIXTURE THEREOF. (R)NA IS A SUBSTITUENT IN WHICH THE FOLLOWING RELATIONSHIP EXISTS: IF N IS - Z MAY BE0 BROMINE, IODINE, FLUORINE. 1 OXYGEN, SULFUR, SELENIUM. 2 NITROGEN, ARESENIC. 3 CARBON. AND WHEREIN R IS SELECTED FROM THE GROUP CONSISTING OF HYDROGEN; ALKYL GROUPS OF 1 TO 18 CARBON ATOMS IN ANY OF THEIR ISOMERIC FORMS, PROVIDED THAT WHEN Z IS OXYGEN THE ALKYL GROUPS FROM WHICH R MAY BE SELECTED CONTAIN FROM 6 TO 18 CARBON ATOMS; SUBSTITUTED ALKYL GROUPS OF 1 TO 18 CARBON ATOMS WHEREIN THE SUBSTITUTENTS ARE SELECTED FRM THE GROUP CONSISTING OF FLUORINE, CHLORINE, BROMINE, IODINE, SULFUR, OXYGEN, PHOSPHOROUS, NITROGEN, AND SILICON; ALICYCLIC GROUPS CONTAINING FROM 5 TO 18 CARBON ATOMS; HETEROCYCLIC GROUPS CONTANING FROM 5 TO 18 CARBON ATOMS WHEREIN THE HETERO ATOM(S) IS SELECTED FROM THE GROUP CONSISTING OF OXYGEN, SULFUR, NITROGEN, PHOSPHOROUS, AND SILICON; AND AROMATIC AND ARALKYL GROUPS CONTAINING FRM 6 TO 18 CARBON ATOMS. THE ABOVE DESCRIBED COMPOUNDS HAVE UTILITY AS FUNGICIDES, BACTERICIDES. INSECTICIDES AND PESTICIDES.

United States Patent US. Cl. 260-455 R 11 Claims ABSTRACT OF THE DISCLOSURE A compound selected from the group consisting of compounds of the formula wherein X is ahalogen-chosen from the group consisting of fluorine,chlorine bromine, and iodine, and mixtures thercOfj-"(RMA is a substituent in which the following relationshi exists:

If n is Z may be- 0 -L Bromine, iodine, fluorine. 1 Oxygen, sulfur, selenium. 2 Nitrogen, arsenic. 3 Carbon.

and wherein R is selected from the group consisting of hydrogen; alkyl groups of 1 to 18 carbon atoms in any of their isomeric forms, provided that when Z is oxygen the alkyl groups from which R may be selected contain from 6 to 18' carbon atoms; substituted alkyl groups of 1 to 18 carbon atoms wherein the substituents are selected from the group consisting of fluorine, chlorine, bromine, iodine, sulfur, oxygen, phosphorus, nitrogen, and silicon; alicyclic groups containing from 5 to 18 carbon atoms; heterocyclic groups containing from 5 to 18 carbon atoms where in the hetero atom(s) is selected from the group consisting of oxygen, sulfur, nitrogen, phosphorous, and silicon; and aromatic and aralkyl, groups containing from 6 to 18 carbon atoms. p

The above described compounds have utility as. fungicides, bactericides, insecticides and pesticides.

ing of fluorine, chlorine, bromine, and iodine and mixtures 3,824,268 Patented July 16, 1974 thereof (R),,Z is a substituent in which the following relationship exists:

If n is- Z may be- 0 Bromine, iodine, fluorine. 1 Oxygen, sulfur, selenium. 2 Nitrogen, arsenic. 3 Carbon.

and wherein R is selected from the group consisting of hydrogen; alkyl groups of 1 to 18 carbon atoms in any of their isomeric forms provided that when Z is oxygen the alkyl groups from which R may be selected contain from 6 to 18 carbon atoms; substituted alkyl groups of 1 to 18 carbon atoms wherein the substituents are selected from the group consisting of fluorine, chlorine, bromine, iodine, sulfur, oxygen, phosphorus, nitrogen, and silicon; alicyclic groups containing from 5 to 18 carbon atoms; heterocyclic groups containing from 5 to 18 carbon atoms wherein the hetero atom(s) is selected from the group consisting of oxygen, sulfur, nitrogen, phosphorus, and silicon; and aromatic and aralkyl groups containing from 6 to 18 carbon atoms.

In a preferred embodiment of the invention, Z is sulfur, X is chlorine, and R is an alkyl group of 1 to 12 carbon atoms, preferably of 1 to 5 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, and tert-butyl, most preferably of 1 carbon atom, methyl.

There is further provided a process for producing the aforementioned compounds by reacting a perhalocoumalin with a nucleophile in the presence of a base, as shown by the equations below:

Z (R) u+base-HX wherein R, n, and X are as hereinbefore defined, provided that when n is 0, X is selected from the group consisting of fluorine, chlorine, and bromine, and the following relationship exists:

If X isp Z may bef- Fluorine Chlorine, bromine, iodine. Chlorine Bromine, iodine. Bromine Iodine.

The compounds so prepared exhibit a wide spectrum of pesticidal activity.

Any base which itself is not a strong nucleophile precursor may be used as a coreagent. Thus tertiary amines may be used, and are the preferred class of bases, but a secondary or primary amine can be used if it is a relatively weak nucleophile precursor in comparison with the primary reacting species. Similarly, alkali or alkaline earth hydroxides, basic alkali salts, alkoxides, and salts of strong bases and weak acids may be used, provided their nucleophilicity is low compared to that of the reactant species.

A secondary amine which is a relatively strong nucleo phile precursor may be used as the reactant species, and the reaction will proceed inasmuch as secondary amines act as both nucleophile precursors and bases, as illustrated by the equation shown below:

The perhalocoumalin is dissolved in a solvent, usually under ambient conditions, before it is made to react with the nucleophile precursor. In general, any polar or nonpolar solvent may be used. However, it is not desirable to use a solvent which itself will form a strong nucleo phile with the base (such as, e.g., alcohols, amines) to avoid possible competing reactions.

The preferred solvents are ethers, e.g. tetrahydrofuran, diethylether, and the like. Other suitable solvents include benzene, acetone, methylene chloride, carbon disulfide, dimethylsulfoxide, and the like.

Once the perhalocoumalin is dissolved, it is made to react with the nucleophile precursor, and base. When one is preparing the mono-substituted perhalocoumalin, about 1 mole of perhalocoumalin is reacted with each mole of nucleophile precursor and with an excess of base though it is preferred to use a substantially equimolar amount of perhalocoumalin and nucleophile precursor. When one is preparing the tri-substituted derivative of glutaconic acid, about 1 mole of perhalocoumalin is reacted with 3 or more moles of nucleophile precursor and 2 or more moles of base, though it is preferred to use about 3 moles of nucleophile precursor for every mole of perhalocoumalin.

During the addition the temperature of the reaction mixture is maintained at to 180 degrees centigrade, usually by cooling. A more preferred range is from 0-30 degrees centigrade, and an even more preferred range is from 20'30 degrees centigrade.

Pressure other than atmospheric is not required for this reaction. However, higher than atmospheric pressure may be used, when the nucleophile precursor is a gas at the reaction temperature.

Generally, the nucleophile precursor is added to the perhalocoumalin, followed by the addition of the base. However, where convenient, one may add the perhalocoumalin to the nucleophile precursor, and then add the base; alternatively, one may first add the base to the perhalocoumalin, and then add the nucleophile precursor thereto, and this method is preferred e.g., when the nucleophile precursor is a gas. When working with secondary amines, which act as both nucleophile precursors and bases, one preferably proceeds by adding them to the perhalocoumalins.

The reaction takes from about minutes to 24 hours, being dependent upon the reactivity of' the nucleophile generated from the precursor, the concentration of the nucleophile precursor, and the concentration of the per halocoumalin. Often, the reaction rate is fast and it is completed upon the mixing of the reagents. After the addition is completed the reaction slurry is filtered and the solvent evaporated from the filtrate or the solvent can be evaporated, first and the resulting mixture triturated with water and the solids filtered oif and dried. If the coumalin derivatives is a liquid it can be isolated by filtration of the reaction slurry followed by evaporation of the solvent and distillation. Solid products may be purified by recrystallization from a solvent such as hexane, benzene, ethyl acetate, chloroform and the like.

In addition to making the tri-substituted derivatives of glutaconic acid in the manner described above, in which all of the (R),,Z groups are identical, one may alternatively make the mono-substituted perhalocoumalin using one nucleophile precursor, and'then-subject the monosubstituted perhalocoumalin to reaction with another nucleophile precursor. The equations presented below illustrate this.

Once the substituted perhalocoumalin products are made, various additional useful derivatives can be obtained. For example, 6-methylthio-3,4,'5-trichloro-2H- pyran-Z-one may be oxidized to the sulfone or sulfoxide,

as illustrated below:'

CH3 S OH: O 0

01- CHI 012 C1-- 0 p 2CH CO H ZCHgCOzH The compounds of this invention are useful as chemical intermediates. They are also useful as fungicides, bactericides and, pesticides, as illustrated in Examples 1333.

The following examples are presented as illustrative of the invention, and are not deemed to be limitative thereof. Unless otherwise specified, parts are by weight and temperatures are in degrees centigrade.

EXAMPLE 1 To a solution of 23.4 parts of perchlorocoumalin and 10.1 parts of triethylamine (in parts of diethylether) Were gradually added 5.0 parts of methyl mercaptan. The addition took place over a period of about 30 minutes and during said addition the temperature was maintained at 2030 degrees centigrade. After completion of the addition, the solvent was evaporated and the residue was triturated with water, which Water dissolved the amine hydrochloride and left behind the substituted coumalin. Said substituted coumalin was then recrystallized from hexane, quantitatively yielding yellow crystals which melted at 8 8-895 degrees centigrade. Elemental analysis of the product disclosed that it contained 29.38 percent carbon, 1.23 percent hydrogen, 43.5 percent chlorine, and

12.95 percent sulfur, indicating that the compound had the formula S CII'IS Cl Y EXAMPLES 2-11 In Examples 2-11 the basic procedure specified in Example 1 was followed, but different reactants and/or dif-. ferent concentrations of reactants were used, as specified in Table I.

In Examples 14-34, substituted perhalocoumalin compounds and derivatives thereof were subjected to tests to determine whether they possessed pesticidal activity. The fOllOwing test methods were used:

SPRAY TESTS (FUNGICID'ES) Early Blight Tomato plants were sprayed with 100 milliliters of the chemical to be tested, dried, inoculated with spores of Alterarnaria solani, and incubated in a moist chamber at 70 degrees Fahrenheit for 24 hours. Control plants were not sprayed with the chemical. Percent control was determined by the formula:

(number of spots which develop on leaves of untreated tomato plantnumber of spots which develop on leaves of treated plant) number of spots which develop on leaves of untreated plant Mildew Ten day old tendergreen bean plants were allowed to take natural infection of Erysiphe polygoni from older infected plants. After the infection began to show on the leaves, the plants were sprayed with the chemical to be tested, dried, and kept in a greenhouse. Control plants were subjected to the aforementioned natural infection and kept in a greenhouse. When the control plants developed the disease, the test plants were removed from the greenhouse and inspected for infection.

SOIL FUNGICIDE TESTS Pythium Test Soil naturally infested with Pythium species was treated with the chemical solution to be tested and allowed to stand 3 days before planting. Plastic pots 3.5 inches x 3.0 inches were filled with the soil, and the chemical was applied to the soil therein by drenching. After 3 days, ten pea seeds, Perfection variety, were planted in each pot. Percent emergence was recorded.

Rhizoctonia Test Sterilized soil was inoculated with Strain #85 of Rhizoctonia solani, placed in 3.5 inches x 3.5 inches plastic pots, drenched with the chemical to be tested, and allowed to stand 3 days. Thereafter 5 Tendergreen bean seeds were planted in each pot. The number of plants developing infection was recorded.

Fusarium Test Sterilized soil was inoculated with F usarium oxysporum lycopersici, and treated with the chemical to be tested. Three days thereafter, five small tomato seedlings were planted in the soil. Fifteen days after said planting, the number of plants showing infection was recorded.

Sclerotium Test Sterilized soil was inoculated with Sclerotium rolfsii, treated with the chemical to be tested, and incubated in moist chambers at 70 degrees Fahrenheit for three days. Perfection variety peas were then planted in said soil, and the percent emergence was recorded.

Nematode Test Sterilized soil was inoculated with galls formed by Meloidogyne incognita on tomato roots, treated with the chemical to be tested, and allowed to stand for two or three days until it was dry enough for mixing. In such soil cucumber seeds were then planted, and the roots thereof were examined to days after planting for infection.

SPRAY TESTS (INSECTICIDES) Aphid Test Ten-day-old Nasturtium plants were infested with black bean aphids (Aphids fabae Scop.) so that the first two 8 leaves had from 50-100 aphids, sprayed with the chemical to be tested, and caged in a piece of ftubing which is coated with talcum powder to prevent the escape of the aphids. Mortality was recorded by counting the number of dead aphids.

Mite Test Young pole lima bean plants (Sieva variety) were infested with 50 to adult mites (Tetranyehus telarius L. on both primary leaves, sprayed 24 hours thereafter with the chemical to be tested, and placed in the greenhouse for from 24 to 48 hours, after which mortality was recorded by counting the number of dead mites.

Mexican Bean Beetle and Army WormTests Primary leaves of lima bean plants were excised, dipped into a solution of the chemical to be tested, and dried. Either 5 larvae (fourth instar) of the Mexican bean beetle (Epilachna varivestis Muls.) or five larvae (second instar) of the Southern Armyworm (Prodenia eridania Cram), depending upon the test to be performed, were placed thereon, and the leaves were so enclosed that the insects could not escape. Mortality was recorded by counting the number of dead larvae, and'the percent leaf consumed by the larvae was estimated.

House Fly Test Newly hatched adult house flies (Musca domestica L.) were, while under the action of carbon dioxide, immersed in the chemical solution to be tested, shaken for a few seconds, and screened out into a paper cup containing filter paper which was dipped in sugar solution, said cups then being covered to prevent escape of the flies. Ten flies were used per treatment. Data was taken on the number of fiies killed in two hours, and killed in; 24 hours.

Bactericidal Test The bacteria to be tested were grown on agar slants for 20 hours. To a mixture of the chemical to be tested and nutrient agar was added two drops of the bacterial suspension, and this mixture was shaken and then poured onto sterilized Petri plates. The plates were incubated for 24 hours, and the bacterial growth noted.

EXAMPLE 14 The perhalocoumalin derivative of the formula EXAMPLE 15 The perhalocoumalin derivative of the formula SI(CH;) CHa exhibited complete control of the bacteria Pseudomonas phaseolicola (Gram at a concentration of 255 parts 9 per million, and at a concentration of 1000 parts per million killed 100 percen't of the houseflies within 24 hoursv, ,EXAMPLE 16 The perhalocoumalin derivative of the formula /CH; some .s C 01 O J :4 i i i 1 exhibited completecontrol of the-bacteria Staphylococcus aureus (Gram and Pscudomonas phaseolicola (Gram at concentrations of 255 parts per million and 76 parts per million, respectively, and at a concentration of 1000 parts per million killed 100 percent of the housefiies within 24 hours.

EXAMPLE 17 p The perhalocoumalin derivative of the formula s wnmcrn exhibited complete control 'ofStaphyloccocus aureus (Gram and Pseudomonas phaseolicola (Gram at a concentration of 255 parts per million. At a concentration of 1000 parts per'million, it killed 20 percent of the southern armyworm, and at the same concentration it killed 100 percent oithe houseflies within 24 hours.

EXAMPLE 18 The perhalocoumalin derivative of the formula CPA Cl w p t1 exhibited complete control of Staphylococcus aures (Gram Pseudomonas phaseolicola (Gram and Xanthomonas phaseoli (Gram at concentrations of 255, 38, and 255 parts perimillion, respectively. At 1000 parts per million concentration it killed 100 percent of the mites, and at the same concentration killed 100 percent of the housefiies within two hours.

EXAMPLE 29 The perhalocoumalin derivative of the formula I Cl exhibited percent control of Pyrhium at a concentration of 64 pounds per acre. It killed 29 percent of the aphids and percent of the mites at concentrations of 1000 and 290 parts per mililon, respectively. At a concentration of 1000 parts per million it killed percent of the houseflies within two hours.

EXAMPLE 21 The perhalocoumalin derivative of the formula killed 30 percent of the aphids and 70 percent of the mites at a concentration of 1000 parts per million; At the same concentration it killed 100 percent of the fiies within two hours.

EXAMPLE 22 The perhalocoumaline derivative of the formula exhibited complete control of Pythium and Sclerotium at concentrations of 64 and 16 pounds per acre, respectively. It killed 38 percent of the aphids at a concentration of 1000 parts per million.

EXAMPLE 23 The perhalocoumaline derivative of the formula killed 40percent of the Southern armyworm'and 100 per-- cent-of theMexic'an bean beetle at concentrations of 1000 and 500 parts per million, respectively.

, EXAMPLE 24 The perhalocoumalin' derivative of the formula 0 0 onto JCH -O( Jl=CC1H3-OCHa OCHa killed 60 percent of the Mexican bean beetle at a concentration of 1000 parts per million.

t1 1 1 2v EXAMPLE 25 EXAMPLE 30 The perhalocoumalin derivative of the formula The perhalocoumalin derivative of the formula iii killed 100 percent of the Mexican bean beetles and per- CITQZO cent of the aphids at concentrations of 1000 and 250 I parts per million, respectively. 10 p v exhibited complete control of Sclerotium at a concentra- EXAMPLE 26 tion of 64 pounds per acre. It killed 100 percent of the The perhalocoumalin derivative of the formula housefiies within two hours and 100 percent of the mites CH3 F at a concentration of 1000 parts per million; 0 EXAMPLE 31 l The perhalocoumalin derivative of the formula C1 Cl O exhibited complete control of Sclerotium, Staphylococcus G1- at a concentration of 64 pounds per acre. At concentrations of 255 and 38 parts per million, respectively, it ex- 1 hibited complete control of the bacteria Staphylococcus hibi d complete control of Pyzhium, Rh'izoctonia, dwells (Gram and Xalllhomomm phaseoli (Gram Sclerotium, and Staphylococcus aureus (Gram at concentrations of 64 pounds per acre, 64 pounds per acre, 64 EXAMPLE 27 pounds per acre, and 255 parts per million, respectively. 30

The perhalocoumalm derivative of the formula EXAMPLE 32 The perhalocoumalin' derivative of the formula ocna Cl 35 ?I\ O H: Cl =0 01-- O l C1 \):O

4O exhibited complete control of Rhizoctonia, Staphylococcus aureus (Gram Pseudomonas phaseolicola (Gram and Xanthomonas phaseoli (Gram at concentrations of 64 pounds per acre, 255 parts per million, 76 parts per million, and 76 parts per million, respectively.

exhibited complete control of Staphylococcus aureus (Gram and Pseudomonas phaseolicola (Gram at concentrations of 255 and 76 parts per million respectively. It killed 42 percent of the mites at a concentration of EXAMPLE 28 1000 parts per million. The perhalocoumalin derivative of the formula EXAMPLE 33 SIOPCH The perhalocoumalin of the formula I CIK H o1 )=o 01 T l 01- =0 c1 v exhiblted complete control of Sclerotium, Staphylococcus aureus, (Gram Pseudomonas phaseolicola (Gram and Xanthomonas phaseoli (Gram at concentrations of 64 pounds per acre, 255 parts per million, 76 parts per million, and 255 parts per million, respectively. It killed 100 percent of the mites at a concentration of 250 parts per million, and it killed 50 percent of the'houseflies within 24 hours at a concentration of 1000 parts per million.

exhibited complete control of Staphylococcus aurcus (Gram Escherichia coli (Gram Pseudomonas phaseolicola (Gram and Xanthomonas phaseoli (Gram at concentrations of 255, 255, 76 and 76 parts per million respectively. It killed 65 percent of the aphids, 100 percent of the mites, and 50 percent of the houseflies within 24 hours at a concentration of 1000 parts per mil- EXAMPLE 29 a lion. The perhalocoumalin derivative of the formula 65 EXAMPLE 34 s CrmHzm The perhalocoumalin derivative of the formula 0on1. (ll-n 1 v exhibited complete control of Pythium and Sclerotium at a concentration of 64 pounds per acre. exhibited complete control of Fusarium and Pseudomonas phaseolz'caola (Gram at concentrations of 64 pounds per acre and 255 parts per million, respectively. It killed 50 percent of the aphids at a concentration of 1000 parts per million.

What is claimed is:

1. A compound of the formula (a) X is chlorine;

(b) R is selected from the group consisting of straight or branched chain alkyl of 1 to 6 carbon atoms, phenyl, benzyl and cyclohexyl.

3. The compound of Claim 2, wherein R is straight or branched chain alkyl of 1 to 6 carbon atoms.

4. The compound of Claim 2, wherein R is alkyl of 1 to carbon atoms.

5. A compound according to Claim 1, wherein R is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, secbutyl, isobutyl and tertiarybutyl.

6. The compound of Claim 4, wherein R is methyl.

7. A compound according to Claim 1, wherein R is selected from the group consisting of phenyl and benzyl.

8. A compound of Claim 1 of the formula 0 0 ll it CHaS -CHCCI=C O1- SCH:

S CH

14 9. A process for making of a compound of the formula:

0 X X 0 RS dork J SR R wherein:

(a) R is selected from the group consisting of hydrogen, straight or branched chain alkyl of 1 to 6 carbon atoms, CH OH. SH, phenyl, benzyl, cyclohexyl and -CH CH OH;

comprising the step of reacting with a compound of the formula RSH in the presence of a base which is more weakly nucleophilic than the RSH compound.

10. A process according to Claim 9 wherein R is straight or branched chain alkyl of 1-6 carbon atoms.

11. A process according to claim 9 wherein R is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, sec butyl, isobutyl and tertiary-butyl.

References Cited UNITED STATES PATENTS 3,528,995 9/1970 Mark at al'. 260-3435 DONALD G. DAUS, Primary Examiner A. M. TIGHE, Assistant Examiner US. Cl. X.R.

260-445, 470, 480, 482 P, 484 P, 485 H, 485 F, 502.6, 534 M, 534 S, 544 F, 544 Y, 561 S, 561 N, 593 H, 609 R, 935, 999; 424212, 279, 297, 301, 313, 314, 320, 331, 335

P194050 UNHED STATES PATENT @FFICE (5/69) 7. A CEllFlCATE U5 EEC'HGN Patent No. 5,824,268 Dated July 16, 1974 Q Q Victor Mark and Leon Zengierski It is certified that error appears in shove-identified. patent and that said Letters Patent are hereby corrected as shown "below:

Column 3, line 9, that part of the formula reading R \NHJ-U.

R/ should read R Y .NHHX.,, Column 6, line 52 "inidcating should read indicating a. Column 8, line 9 "L0" should read L.) Column 9, line 7, "SCH C" should read SCH CH o Column 10, line 1, "Example 29" should read Example 20 llne l6 "mililon" should read M million line 36, "perhalocoumaline" should read perhalocoumalin line 52, "perhalocoumaline" should read perhalocoumalin line 71,

"OCH should read OCH Column ll line 23, "of Sclerotium, Stapfiylococcus" should read of Pythium and Rhizoctonia Column 11,

line 48, "80 C should read SH C Column 12,, line 50, that part of the formula reading I 9% H C1 u should read" "0 Cl L0 l Cl Signed and sealed this 22nd day of October 1974.

(SEAL) Attestz McCOY Ma GIBSON JR, co MARSHALL DANN Arresting Officer Commissioner of Patents 

